Excess Weight Linked to Cardiotoxicity in Breast Cancer

Association seen whether anthracyclines were given alone or with trastuzumab

Action Points

In patients with breast cancer, overweight and obesity were significantly associated with a greater risk of developing cardiotoxicity after treatment with anthracyclines and a regimen of sequential anthracyclines and trastuzumab (Herceptin), according to an unadjusted meta-analysis.

Note that while obesity has increased more rapidly among cancer survivors than in the general population, researchers could not separate the contributions of obesity-related cardiovascular risk factors, such as diabetes and hypertension, from that of obesity itself to the increased risk of treatment-related cardiotoxicity.

In patients with breast cancer, the combination of overweight and obesity was significantly associated with a greater risk of developing cardiotoxicity after treatment with anthracyclines and a regimen of sequential anthracyclines and trastuzumab (Herceptin), according to researchers.

A network meta-analysis based on 15 studies showed that in 8,745 overweight or obese women with a body mass index (BMI) greater than 25 kg/m2, the pooled odds ratio for cardiotoxicity was 1.38 (95% CI 1.06 to 1.80; I2 = 43%), Charles Guenancia, MD, PhD, of Centre Hospitalier Universitaire de Dijon in France, and colleagues reported online in the Journal of Clinical Oncology.

In 2,615 women who were obese, the pooled odds ratio for cardiotoxicity was 1.47 (95% CI 0.95 to 2.28; I2 = 47%), and in 2,708 patients who were overweight, it was 1.15 (95% CI 0.83 to 1.58; I2 = 27%).

"Our findings in a largely unadjusted analysis suggest that overweight and obesity are risk factors for cardiotoxicity from treatment with anthracyclines and sequential anthracyclines and trastuzumab," Guenancia and colleagues wrote. "A careful assessment of cardiovascular risk factors is crucial to improve risk stratification for cardiotoxicity in patients with breast cancer who are treated with anthracyclines and trastuzumab."

These associations were independent of whether anthracyclines were given alone or with trastuzumab, and were also independent of the definitions of cardiotoxicity, overweight, or obesity, the researchers noted.

They emphasized that more studies are needed to determine the independent predictive value of obesity on cardiotoxicity as well as to identify potential therapeutic targets to reduce increased risk.

While there was no evidence of publication bias, the researchers said that they "could not separate the contributions of obesity-related cardiovascular risk factors, such as diabetes and hypertension, from that of obesity itself."

A second study reporting on trends in obesity prevalence in adult survivors of cancer revealed that in the last two decades, obesity increased more rapidly among cancer survivors than in the general population.

Results from the U.S. National Health Interview Survey, 1997 to 2014, showed that the prevalence of obesity increased consistently from 22.4% in 1997 to 31.7% in 2014 in cancer survivors and from 20.9% to 29.5%, respectively, in adults without a history of cancer. "Our findings suggest that obesity is a growing public health burden for cancer survivors, which requires attention," Heather Greenlee, ND, PhD, of Columbia University in New York City and colleagues reported online, also in the Journal of Clinical Oncology.

"Although it is well known that unfavorable lifestyle factors may contribute to the overall increase in obesity, future research should identify and act on modifiable risk factors that may be responsible for the steeper obesity trends in cancer survivors."

The survey -- which consisted of a population-based nationally representative sample of 538,969 non-institutionalized U.S. adults age 18 to 85 -- included those with and without a history of cancer. The results showed that those getting fatter the fastest were women, survivors of colorectal and breast cancers, and non-Hispanic blacks.

"These findings call for public health planning of effective and scalable weight management and control programs for cancer survivors, especially for breast and colorectal cancer survivors and for non-Hispanic blacks," Greenlee and colleagues emphasized. Obesity after a diagnosis of specific cancers has been associated with worse prognosis, they noted.

Both are with Harvard Medical School and the Harvard T.H. Chan School of Public Health in Boston.

"There is a clear difference in the effect estimate of BMI on total cancer risk in smokers versus nonsmokers for various reasons, including true causality, confounding, reverse causation, and different mixture of cancers," Song and Giovannucci wrote. "Yet regardless of the reasons, for clinical communication for risk prediction, it is inappropriate to provide a single effect estimate, which would be neither predictive for a smoker, nor a nonsmoker."

The relevance of BMI for a smoker is more complicated than for a non-smoker, the editorial pointed out. For one, smokers tend to have a lower BMI than nonsmokers, thanks to nicotine-stimulated energy expenditure and appetite suppression. However, chronic illnesses such as chronic obstructive pulmonary disease may also play a role in keeping BMI lower in nonsmokers.

Song and Giovannucci pointed to a recent meta-analysis showing that when compared with nonsmokers, past and current smokers had a 14% and 37% increased risk of developing type 2 diabetes, respectively. This risk was elevated even in smokers of normal weight.

"Therefore, from a biologic perspective, high BMI is likely to represent inherently different pathophysiologic alterations in smokers and nonsmokers."

Taking smoking history into account is "critical," Song and Giovannucci said. This is particularly true when considering total cancer burden, they pointed out: "As results are likely different between smokers and nonsmokers -- that is, there is a strong effect modification by smoking -- combining the two strata to obtain a pooled estimate is inherently inappropriate from an epidemiologic perspective."

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